Nearly 4,000,000 bone grafting procedures are performed globally every year at a cost of 2.3 billion dollars and it is projected to reach 3.4 billion dollars in 2023 [30]; around 600,000 of these are performed in the US [31].
Bone grafts are used to fill large volumes of bone loss from fracture, traumatic injury or other physical disorder that affects bone architecture and function in the body. Such types of bone loss lead to formation of critical size defects (CSD), which without grafting or other intervention usually lead to non-union. Bone grafts must have adequate mechanical properties to support new bone formation in the defect and be osteogenic and resorbable to maintain continuity of support during bone regeneration [32]. Currently, allograft, autografts and in some cases xenografts are being used for CSD treatment. However, these materials can cause disease transmission, donor site morbidity, and acute immunological responses that can lead to bone resorption and graft rejection [33]. Also, resources for allografts and autografts are limited. Therefore, there is a vital need for new bone substitutes that can rapidly heal these defects to reduce patient discomfort and medical care costs.
The essential component for an acceptable treatment approach for healing fractures is that the treatment be provided as soon after the bone defect has occurred, and that it facilitates turnover of bone within 4-8 weeks.
Current approached to bone repair have been described to involve the fabrication of a scaffold using a 3-D printing technique. These fabricated scaffold may then be implanted into a patient at a site in need of repair of a small to large bone fracture. Conventional methods that are being used for fabrication of 3D scaffolds are labor-intensive, time-consuming, and do not provide precise control over the scaffold's architecture. Rapid prototyping (RP) is a technique that can be divided into the additive and subtractive method. Additive rapid prototyping (ARP) is more popular because of its ability to create further complex shapes and hollow structures. ARP is increasingly used for tissue engineering [38] and craniofacial reconstruction [37]. Currently in craniofacial reconstruction, APR technology is used for preoperative treatment planning by fabricating a 3D shape of the site of surgery and practicing the surgery on the model [37].
ARP is a broad category that includes many different methods including stereolithography, fused deposition modeling, direct metal laser sintering, laminated object manufacturing, electron beam melting, selective laser sintering, laser engineered net shaping, and 3-dimensional printing (3DP). 3DP does not require heat for its functionality which makes it useful for cell or growth factor incorporation. This feature made 3DP an attractive method for tissue engineering [39]. Robocasting or direct ink writing (DIW) is a subcategory of 3DP that is based on a computer aided fabrication method that uses extrusion of the “ink” while moving in all three axes to make a 2D layer. By adding these 2D layers on top of each other, a 3D object can be created. The robocaster allows precise control of micro patterning by determining the dimensions of filaments, the size and shape of pores and the percentage of porosity of the scaffold [40-42].
Although extensive research has been conducted on suitable biomaterials for 3DP, there are few well-established biomaterials that can be 3D printed and implanted in the body [42]. These materials include bioceramics such as bioglass, TCP, and HA, and biopolymers such as PLA, PGA, and PLGA.
Previously described techniques for achieving bone fracture repair include the use of fixative metals, or the use of resorbable biopolymers. The use of either fixative metals or resorbable polymer materials in bone repair suffers from several disadvantages, including, among other things, a lack of bone bioactivity of these materials. This ultimately results in prolonged patient healing times and, many times, incomplete bone healing results to the patient. In addition, and because metal implants do not resorb into the body, the implant remains fixated in the patient's bone. In addition, optimal complete bony replacement at the bone defect (fracture) site in the patient does not occur.
As noted, biopolymers have also been proposed and used for repair of bone fracture. However, currently described biopolymers for this use in healing bone fracture lacks the needed strength to support rapid bone turnover, among other drawbacks.
Existing 3-D printing methods have also been found inadequate for the repair of bone fracture, primarily because current methods require significant added lead time for fabrication of a suitable scaffold before implant at a fracture site may be made. Moreover, 3-D methods previously described do not provide alternative approaches to a pre-fabricated scaffold implant for bone repair, or of a suitable, biocompatible and visco-elastic material suitable for bone cell integration and bone formation.
Craniofacial reconstruction surgeries present a particularly challenging problem concerning repair of bone because of the complex anatomy of this region and its proximity to the vital tissues, among other challenges. These surgeries have required the fabrication of a custom implant prior to surgery. Such pre-fabrication techniques for a bone graft fabrication are described, for example, in US PUB 20150054195 (Grey). Fabrication of a custom implant is time consuming, and creates a delay in when a patient may undergo a corrective/reconstructive surgery. Delay in surgical intervention is recognized as creating an increased risk that the surgery will not be successful and/or will provide less than patient acceptable results. Therefore, a new surgical method is needed to treat bone defects with the least possible delay, while at the same time not sacrificing any significant loss in bone repair precision or implantation/repair success rate.
The medical arts remain in need of alternative and improved materials and techniques for providing bone fracture repair that are sufficiently strong and suitable for immediate bone treatment without the need for a pre-fabricated scaffold, and that have improved complete boney replacement at a fracture site than that achievable with metal implants. promote not adapted for use in direct printing of materials into defects for immediate treatment of the fracture/defect site.